From Puberty to Menopause: Microbiome-Driven Metabolic Reprogramming Across the Female Life Course

The human microbiome has emerged as a key regulator of endocrine, immune, and metabolic homeostasis, influencing host physiology through microbial metabolites, epithelial barrier integrity, inflammatory signaling, and endocrine communication. Concurrently, advances in reproductive endocrinology have demonstrated that female reproductive transitions are characterized by profound physiological adaptations extending beyond reproductive tissues to systemic metabolism. Despite these advances, research remains fragmented across individual diseases, organs, microbial niches, or isolated molecular pathways, limiting the development of an integrated understanding of female metabolic health. Recent progress in longitudinal cohort studies, multi-omics technologies, computational biology, and systems endocrinology provides an unprecedented opportunity to investigate how cumulative host–microbiome interactions shape metabolic trajectories across the female life course. Integrating these disciplines can uncover shared biological mechanisms underlying apparently distinct metabolic disorders while facilitating earlier diagnosis, improved risk prediction, and stage-specific preventive and therapeutic strategies.

Women's metabolic disorders are traditionally investigated and managed as separate clinical conditions, despite increasing evidence that many originate from interconnected biological processes operating across the reproductive life course. Puberty, reproductive maturation, pregnancy, and menopause represent critical developmental transitions during which endocrine adaptation, immune regulation, microbial ecology, and environmental exposures undergo dynamic remodeling. These biological changes may progressively reprogram metabolic function, shaping susceptibility to insulin resistance, dysglycemia, obesity, and cardiometabolic disease later in life. However, research remains fragmented across individual diseases, organs, and molecular pathways, limiting a comprehensive understanding of how these interacting systems collectively influence long-term metabolic health. This Research Topic aims to establish a life-course framework for women's metabolic health by recognizing reproductive transitions as biological windows of metabolic reprogramming mediated through host–microbiome interactions. We seek contributions that move beyond descriptive associations to investigate the mechanistic interplay among the microbiome, endocrine signaling, immunometabolism, epithelial barrier function, microbial metabolites, genetics, epigenetic regulation, and environmental factors. By integrating microbiome biology, endocrinology, immunometabolism, systems biology, and precision medicine within a life-course framework, this collection aims to advance mechanistic understanding, identify predictive biomarkers, and accelerate preventive and personalized strategies for improving women's metabolic health across reproductive transitions.

This Research Topic welcomes Original Research, Clinical Trials, Systematic Reviews, Reviews, Mini Reviews, Methods, Perspectives, and Hypothesis and Theory articles that advance mechanistic, translational, computational, or clinical understanding of microbiome-associated metabolic regulation in women. We invite contributions addressing, but not limited to, microbiome dynamics during puberty, reproductive aging, pregnancy, menopause, Polyendocrine Metabolic Ovarian Syndrome (PMOS), and emerging metabolic concepts, gestational diabetes, insulin resistance, obesity, metabolic syndrome, endocrine regulation, host–microbiome–immune interactions, microbial metabolites, intestinal and reproductive tract microbiomes, epithelial barrier biology, inflammation, immunometabolism, multi-omics integration, epigenetic regulation, biomarker discovery, predictive modeling, pharmacomicrobiomics, nutrition, lifestyle interventions, and precision medicine.

Given the interdisciplinary nature of this Research Topic, studies integrating multiple biological systems across the female life course are encouraged, such as longitudinal cohort studies, functional experimental investigations, intervention studies, systems biology approaches, and multidisciplinary research that moves beyond descriptive associations to elucidate causal mechanisms and generate clinically actionable insights capable of improving metabolic health across the female life course.